Primary Amebic Meningoencephalitis -- North Carolina, 1991

During September 1991, two children in North Carolina died
from primary amebic meningoencephalitis (PAM), a rare and often
fatal illness resulting from infection with Naegleria fowleri. This
report summarizes clinical and epidemiologic information about
these two cases and characterizes N. fowleri infection.
Patient 1

In September 1991, a previously healthy 3-year-old girl was
evaluated by her physician for a 36-hour history of headache and
fever; she was lethargic without focal neurologic or meningeal
signs. Four hours after evaluation, she became disoriented and did
not recognize her parents. When examined at a local emergency
department, she was unresponsive to painful stimuli and had fever
of 101.8 F (38.8 C). Subsequently, she had a generalized seizure,
followed by posturing movements; she was treated with
anticonvulsants and tracheally intubated.

Ceftriaxone was initiated for suspected meningitis. She was
transferred to a children's hospital, where she responded only to
painful stimuli by flexion withdrawal. Computed tomography (CT) of
the head without contrast was normal. No organisms were seen on
Gram or acid-fast stains of cerebrospinal fluid (CSF); CSF
antigen-detection tests were negative for Haemophilus influenzae
type b, group B Streptococcus, S. pneumoniae, Neisseria
meningitidis, and Escherichia coli K1. CSF red blood cell count
(RBC) was 1800 per mm3; white blood cell count (WBC), 8000 per mm3;
glucose, 41 mg/dL; and protein, 950 mg/dL.

Fourteen hours after admission, the patient developed primary
central hyperventilation and anisocoria. Head CT with contrast
revealed generalized meningeal enhancement most prominent in the
basilar cisterns, with mild hydrocephalus and no brain swelling.
Initial bacterial cultures of blood, CSF, and urine were negative.

On the second hospital day, further history revealed that the
family, including the patient, had been swimming in a freshwater
pond 7 days before the patient's hospitalization. A second CSF
specimen obtained 38 hours after admission was xanthochromic with
17 mg/dL glucose, 3200 mg/dL protein, 500 RBC per mm3, and 2400 WBC
per mm3. No amebae were seen on Giemsa stain. There was no evidence
of brain stem function; brain death was diagnosed on hospital day
4.

Additional history during a postmortem conference indicated
that 5 days before illness the patient had been learning to swim at
the freshwater pond. She stayed primarily in shallow areas and had
repeatedly inhaled and swallowed quantities of water.
Patient 2

In September 1991, a previously healthy 4-year-old boy was
admitted to a community hospital with a 3-day history of fever to
102 F (38.9 C) and headache. The child had vomited during the 2
days before admission but had remained alert and intermittently
playful. On evaluation he was febrile with neck stiffness and
positive Kernig's and Brudzinski's signs. CSF contained 77 mg/dL
glucose and 150 mg/dL protein, with 123 RBC per mm3 and 1830 WBC
per mm3. On admission, blood, urine, and CSF cultures were
obtained; ceftriaxone was initiated intravenously. Four hours after
admission, the patient had brief generalized tonic-clonic seizures.
Although anticonvulsant therapy was initiated, he had another brief
generalized seizure, after which he remained agitated and
intermittently disoriented. He was then transferred to a university
medical center.

On admission, additional history revealed that the patient
swam in a grassy marsh 18 days before becoming ill. He was afebrile
but he remained intermittently disoriented; respiratory distress
developed shortly after admission, and a chest radiograph was
consistent with aspiration pneumonitis. His respiratory status
deteriorated, and he was tracheally intubated. Five hours after
admission he developed anisocoria. Head CT showed massive brain
swelling. Treatment included hyperventilation, placement of a
ventriculostomy, and parenteral dexamethasone.

Despite these efforts, the patient continued to deteriorate.
He developed fixed and dilated pupils bilaterally. Spontaneous
respirations ceased, and there was no response to painful stimuli.
Brain death was diagnosed. Cerebellar brain cuttings during autopsy
revealed N. fowleri in the subarachnoid space.

Additional history indicated that the patient had been
swimming in a freshwater lake 5 days before hospital admission.

Editorial Note

Editorial Note: N. fowleri is an ameboflagellate from the family
Vahlkampfiidae, whose members can transform from amebae to
flagellates; either form can cause disease. Although infection with
N. fowleri is rare, cases have been reported throughout the world
(e.g., in Australia, Belgium, Czechoslovakia, Great Britain, India,
Ireland, New Zealand, Nigeria, Panama, Puerto Rico, Uganda, and
Venezuela). During 1991, in the United States, four patients were
reported to have had fatal PAM. N. fowleri is most frequently
isolated from natural and manmade bodies of warm fresh water. Most
cases of PAM occur in previously healthy nonimmunocompromised
children or young adults and have been traced to water-related
activities during hot summer months.

Amebae invade the central nervous system through the
cribriform plate and can be found in the subarachnoid and
perivascular spaces. Disease characteristics include inflammation
of the olfactory bulbs, progressing rapidly to the cerebral
hemispheres, brain stem, posterior fossa, and spinal cord. Symptoms
occur within 7 days of exposure, are indistinguishable from
fulminant bacterial meningitis, and can include headache, fever,
anorexia, vomiting, signs of meningeal inflammation, altered mental
status, and coma. Signs of brain stem compression and seizures may
ensue. Death typically occurs within 72 hours of onset of symptoms.

CSF findings mimic those of bacterial meningitis, with a
predominantly polymorphonuclear leukocytosis and increased protein
and decreased glucose concentrations. Occasionally, amebae may be
seen on Gram-stained smears. Typically, however, PAM is diagnosed
at autopsy. The key to diagnosis during life rests on clinical
suspicion based on history. PAM should be suspected in a previously
healthy patient with history of exposure to fresh, warm water
within 7 days of onset of illness and who has clinical findings
characteristic of bacterial meningitis and predominantly basilar
distribution of exudate by head CT.

If PAM is suspected, a fresh nonrefrigerated specimen of CSF
must be brought directly to the laboratory. If lumbar puncture has
already been done and another cannot be performed, inspection of
the high-velocity centrifuged preparation made for determination of
CSF cell count may be helpful, especially if "atypical mononuclear
cells" are reported; such cells actually may be amebae. Although
culture of the organism on an agar slant or plate containing E.
coli or Enterobacter aerogenes is possible, most laboratories are
not prepared to perform such cultures. Thus, diagnosis depends on
microscopic examination of CSF. CSF should be examined in wet-mount
preparation as well as with fixation and staining. Dilution of 1
drop of CSF with 1 mL of distilled water will allow transformation
of the organism within 1-20 hours from the ameboid to the
biflagellate form. For permanently stained preparations, Masson's
trichrome stain is optimal as it is generally available and readily
demonstrates the ameba's typical nuclear morphology consisting of
a prominent central nucleolus without any chromatin lining the
nuclear membrane (1-4).

Three survivors of PAM have been documented (5-7). Successful
therapy in these cases appeared related to early diagnosis and
administration of intravenous and intrathecal or intraventricular
amphotericin B along with intensive supportive care. One surviving
patient received miconazole intravenously and intrathecally and
rifampin orally (7).

In nearly all instances of infection in the United States,
several other persons swam in the same water at the same time but
did not become ill. The specific behavioral, physiologic, or
anatomic risk factors for disease are unknown. More aggressive
diagnosis and reporting of disease may assist in clarifying risk
factors and in improving therapeutic interventions and possible
strategies for prevention.

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